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In order to induce structural conformation in peptides many scientists have utilized cyclization due to the versatile methods of peptide synthesis and availability of protecting groups which can be orthogonally removed. Constrained peptides have been shown to have improved the biological properties compared to the linear peptides.
Introduction
Conclusion:
Peptide Type of Modification Properties
BID BH3
NOTCH1
DP178(HIV35)
α - Conotoxin N- to C- terminus cyclization Increased stability in human plasma1
Increased protease resistance and serum stability2
Increase binding affinity towards NOTCH transactivation complex3
Increase HIV inhibitory activity as a result of stabilized α-helical conformation4
Hydrocarbon stapling using ring closing metathesis
Hydrocarbon stapling using ring closing metathesis
Side chain to side chain i, i+7 lactam bridge formation
Classic ExamplesLactam Bridge Peptides
Head to tail/ end to side chain cyclization
Backbone Cyclization
Hydrocarbon Stapled Peptides
Lactam bridge formationHydrocarbon stapling usingring closing metathesis
NH
HN
HNN
H
HN
R
R
RR
R
1
2
3 5
O
O
O
O
O4
NH
O
R HN
HN
NH HN
HNLinker1
R2
O
O
O
O OR3
R4
R5
It is scientifically evidenced that constrained peptides in form of stapled or lactam-bridged have attractive biological properties superior to their linear counterparts and introduced a unique technique for studying protein-protein interactions which mediates most of biological actions. In order to further study peptides with these promising properties, BIOSYNTHESIS, INC. has recently launched a peptide conformation screening tool called positional cyclization scanning. This technique is aimed at identifying the receptor-bound conformation of various biological peptides by constraining specific segment of the peptide and studying its effect on the biological activity.
Applications of Constrained Peptides to Various Biological ProcessesEunice Murage, Ph.D. and Miguel Castro, Ph.D.
Protein Chemistry, Bio-Synthesis, Inc., Lewisville, Texas 75057
For example, cyclic peptides have shown: 1. Enhanced receptor affinity and efficacy 2. Improved cell permeability and enzyme stability
In addition, these constraints provide a conceptual approach towards designing of peptidomimetics.
Toll Free: 800.227.0627 | 972.420.8505Mail: [email protected]
Service across Genomics, Proteomics and Cell Biologywww.biosyn.com
1. Clark et al. Proc Natl Acad Sci USA 2005, 102, 13767–13772.2. Walensky et. al., Science, 2004, 3, 1466-14703. Raymond et. al., Nature 2009, 462, 182-188.4. Judice et. al., Proc. Natl. Acad. Sci. USA. 1997, 94, 13426-13430
References:I would like to thank Ian Flynn and Heidi Fazeli and for design and support.
Acknowledgement:
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